title: 2-Ethoxy-4,5-diphenyl-1,3-oxazine-6-one activates the Nrf2/HO-1 axis and protects against oxidative stress-induced neuronal death.
abstract: Apoptosis or programmed cell death has been suggested as an important mode of neurodegeneration in Alzheimer's disease pathogenesis. The present study explored the neuroprotective effect of 2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one (EDPOO) against H(2)O(2)-induced cell death in rat pheochromocytoma (PC12) cells. We found that H(2)O(2) triggered a range of cellular cascades which leads to cell death, whereas pretreatment of the cells with this oxazine derivative attenuated the extent of apoptosis, as assessed by MTT assay, acridine orange/ethidium bromide staining and caspase-3 expression assay. We further showed that EDPOO exerts its neuroprotective effect by enhancing Hsp-70 level, stabilizing Nrf2 and upregulation of HO-1 and γ-GCS. Moreover, this oxazine derivative regulated cellular redox status via antioxidant enzyme upregulation. The neuroprotective effect of this compound may provide a new potential application for the treatment of neurodegenerative diseases.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D055550:Protein Stability / Q000187:drug effects; D051381:Rats
chemical_list: C559680:2-ethoxy-4,5-diphenyl-1,3-oxazine-6-one; D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D051267:NF-E2-Related Factor 2; D010078:Oxazines; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D053148:Caspase 3; D005721:Glutamate-Cysteine Ligase